Heritable (autosomal dominant) cancers in man offer a system for studying the nature of genetic expression (i.e. cancer cell phenotypes) and the operation of trigger mechanisms for gene expression. In human hereditary tumors the first step is considered to be a mutation (heritable chromosomal change) which occurred in the germinal tissue. The first phase of this planned research has been and will be to study this initial pre-tumor stage present in all heritable (autosomal dominant) cancers. Cells of different types from affected individuals with known heritable disorders will be cultured to determine if specific mutant genotypes can be demonstrated in vitro by abnormal cellular activity before the mutant phenotype is evident in vivo. As this first mutation is specific for one or more tissues, it should be possible to compare the activity (morphologic and metabolic) of cultured cells which have the ability ultimately to show malignant transformation in vivo with those that do not from the same individual. The ultimate objectives of the first phase are: (a) detection of a reliable cell marker for the cultured cell which reliably reflects the presence of a specific autosomal dominant mutation and (b) use of this abnormal cell phenotype to detect carriers of the mutation in high risk families and eventually in the general population.